Bacterial Fc receptors have been identified by their ability to bind to a site within the constant region of various classes and subclasses of mammalian IgG. The Fc region of the IgG antibody molecule is associated with the biological effector properties of the molecule, while the antigenic recognition elements are located in the two identical Fab portions of the antibody. Consequently, the interaction of bacterial Fc receptors with constant region determinants on the heavy chain of IgG does not interfere with the ability of the antibody to recognize its antigen. This property makes these receptors useful as tracers of antibody-antigen interaction.
It is known that streptococci and staphylococci bacteria produce proteinaceous factors that bind the Fc region of specific human and animal immunoglobulins. Such proteinaceous factors are also widely used within the industry for extracting and purifying monoclonal antibodies for subsequent application in diagnostics and immunotherapy.
Protein A, the immunoglobulin G(IgG)-binding protein of Staphylococcus aureus, was identified in 1966. See A. Forsgren and J. Sjoguist, J. Immunol. 97: 822-827 (1966). Immunoglobulin-binding strains of other bacterial species have been described, and especially protein G of group C and G streptococci have been characterized. M. Yarnall et al., J. Gen. Microbiol. 32: 2049-2052 (1986); L. Bjorck and G. Kronvall. J. Immunol. 133: 969-974 (1984); M. Boyle and K. Reis, Bio/Technology 5: 697-703 (1987).
Boyle and Yarnall (U.S. Patent No. 4,883,754) describe a streptococcus derived proteinaceous factor that specifically binds the Fc region of IgG.sub.3 and has a molecular weight of 38 kD. There is also described a separate proteinaceous antigenic factor derived from streptococcus that binds the Fc region of human IgG.sub.1, IgG.sub.2, and IgG.sub.4 having a molecular weight of about 56 kD.
Boyle and Faulmann (U.S. Pat. No. 4,945,157) describe a process for extracting an IgG binding proteinaceous factor, Protein G, from streptococcus. Protein G binds the Fc region of human IgG and reportedly has a molecular weight of about 52 kD.
Boyle and Reis (U.S. Pat. No. 4,977,082) describe a Type VI bacterial receptor for the Fc region of human IgG. The Type VI bacterial receptor has a molecular weight of about 43 kD, and is further characterized in that it binds goat, pig, rabbit, mouse, rat, sheep, cow, and human IgG. Boyle and Reis disclose yet another Type VI bacterial receptor having a molecular weight of about 90 kD and that is present in the culture with the 43 kD protein. The two proteins are separable from other proteins in the concentrated culture supernatant by affinity purification on immobilized goat IgG columns. Both proteins are derived from strains of streptococcus zooepidemicus.